This is a 5-year proposal to study the contribution of reproductive hormones to vaginal immunity in middle adolescent women. It has been established in adult women that the onset of STDs often correlate to specific stages of the menstrual cycle, predominantly when estrogen and progesterone levels are high. Also established is the negative influence reproductive hormones have on innate resistance and acquired immunity at both the systemic and mucosal level.Very little is known, however, about immune reactivity at the vaginal mucosa in middle adolescent women who are at high risk for STIs, and what role(s) reproductive hormones have in that susceptibility. We hypothesize, based on studies in adult women, that adolescent women will have demonstratable vaginal immunity that is negatively influenced by reproductive hormones, potentially resulting in susceptibility to STDs. Furthermore, we hypothesize that STIs or specific factors (sexual activity, bacterial vaginosis, spermicide usage) will trigger definable local immune responses that are similarly influenced by reproductive hormones. To test this hypothesis, we will 1) characterize vaginal immunity longitudinally over a period of 3 years in a large cohort of middle adolescent women through the presence of cytokines, chemokines, antibodies, and innate cellular resistance mechanisms in vaginal secretions (lavages), (2) compare the local immunity to that which is antigen-specific in the peripheral circulation, and 3) correlate the vaginal immunity to the presence of reproductive hormones, microflora colonization, symptomatic infection, and sexual activity. Since the majority of women in the cohort will not have been exposed to STIs, and thus are not expected to express STD pathogen-specific immunity, adolescent immunity will be characterize relative to the yeast Candida albicans, a vaginal commensal and hormone-influenced opportunistic vaginal pathogen, that most individuals (including adolescents) express innate and acquired immunity against. The long term goals will be to use the information of this project together with that from the others within the Core, to develop strategies for the prevention and control of STDs in adolescent women.